Oral squamous cell carcinoma (OSCC) is the most common type of oral neoplasm,accounting for over 90% of all mouth malignancies and 38% of head and neck tumors.Worldwide, OSCC is the eighth most common human cancer, with more than 500,000 newcases being diagnosed every year. Surprisingly, the number of annual deaths for this diseasehas practically not changed in the last 30 years (Funk, G.F.; Karnell, L.H., 2002).This is because invasive surgical treatments (involving both oral cavity and neck) are stillthe only effective way to treat OSCC; thus detection in early stages could dramaticallyimprove cure rates and quality of life by minimizing invasive surgery (Scully, C., 1995). Toimprove diagnosis and prevention, researchers have spent considerable effort to understandwhich genetic and/or environmental changes may be related to this tumor. Althoughenvironmental risk factors associated with development of oral cancer have been sufficientlyunderstood (smoking, alcohol, betel, diet, living habits, etc.), knowledge of the genetic basesin oral carcinogenesis is still a challenging task. OSCC is a result of multiple genesalterations, which are modulated by individual predisposing conditions and environmentalinfluences. Furthermore, in the last ten years a new category of non-genetic events able tomodify gene expression has been massively investigated: the so called ‘epigeneticphenomena’ (Bird, A., 2007).Epigenetic factors are non-genetic phenomena which interfere with genes expression. Suchmodifications pass on successive generations of cells, even if there is no mutation incorresponding genes. Epigenetic events are linked with carcinogenesis when one or more oncogenes/tumour suppressors are directly or indirectly affected such that their expressionand function may be permanently altered (Feinberg, A.P., 2001)Cellular aging, risk factors and, as recently discovered, chronic inflammation via mediators,such as IL-6, may be potential inducers of epigenetic alterations in oral mucosa cells. It is ageneral belief that these alterations would accumulate in the normal-appearing mucosawhile carcinogenesis is in progress, or before any tumor lesion is detected.Three major types of such epigenetic mechanism are currently known: DNA hyper-methylation, histone code changes and RNA interference.

J Oral Pathol Med. 2012 May 3. doi: 10.1111/j.1600-0714.2012.01156.x. [Epub ahead of print] Expression and localization of aquaporin-1 in temporomandibular joint disc with internal derangement. Loreto C, Galanti C, Almeida LE, Leonardi R, Pannone G, Musumeci G, Carnazza ML, Caltabiano R. Source Department of Bio-Medical Sciences, University of Catania, Catania, Italy Department of Dentistry, Faculty of Dentistry, University of Catania, Policlinico Universitario, Catania, Italy Center for Health and Biological Sciences, Pontifical Catholic, University of Panarà, Curitibe, Brazil Department of Surgical Sciences, Institute of Pathology and Cytopathology, University of Foggia, Foggia, Italy Department of Anatomy, Diagnostic Pathology, Forensic Medicine, Hygiene and Public Health, University of Catania, Catania, Italy. Abstract Internal derangement is the most J Oral Pathol Med (2012) Background: frequent arthropathy affecting the temporomandibular joint, where its commonest form is anterior disc displacement with or without reduction. Despite the frequency of the disorder, the biochemical features of displaced discs are still We investigated the expression pattern and localization of unclear. Methods: aquaporin-1, an important channel protein involved in plasma membrane water permeability, in patients with anterior disc displacement (both with and without reduction), with a view to assessing the characteristics of local tissue responses to the microenvironmental changes induced by abnormal mechanical loading of the displaced disc. Protein expression was studied by immunohistochemistry in different areas of discs from 18 patients with anterior disc displacement with or without reduction and in four normal controls. A greater proportion of cells immunopositive for aquaporin-1 were Results: detected in diseased than in normal discs. Whereas protein expression was substantially similar in the different areas of normal discs, a significantly larger number of immunopositive cells were detected in the posterior band of displaced discs without reduction and in the anterior and intermediate bands of These findings suggest that aquaporin-1 is those with reduction. Conclusions: expressed and upregulated in temporomandibular joint with anterior disc displacement (both with and without reduction).

Abstract: The EGFR (epidermal growth factor receptor) a member of the family of transmembrane protein kinase receptors known as the erbB family shows a significant correlation with the presence of metastases and poorly differentiated oral cancer. Aim of the present work is to define the key-role of EGFR in oral cancer prognosis. We have analyzed the EGFR expression on 149 cases of oral squamous cell cancers (OSCC) and we have found that it was poorly expressed in normal oral epithelium, but its expression was significantly increased in OSCCs. Moreover, we have recorded that both pEGFR-Tyr 845 and pEGFR-Tyr 1068 were mainly distributed in high histological grading and in advanced stages. Western blotting has confirmed the total absence of EGFR phosphorylation in normal oral epithelium and the higher level of protein phosphorylation in representative cases of OSCCs. The EGF-R amplification was found by fluorescence in situ hybridization (FISH) in 14% of OSCC; interestingly, EGF-R amplification was mainly observed in OSCC with higher histological grading (G2 and G3) and advanced stage (pT4) sub-groups. Kaplan-Meyer survival analysis suggested that patients with positive pEGFR-Tyr 845 tumors had a worse prognosis and were bad responders to chemotherapy. These results confirm the central role of EGF-R activation status as a prognostic biomarker in OSCC.

The role of sex hormone receptors in human cancer development and progression has been well documented in numerous studies, as has the success of sex hormone antagonists in the biological therapy of many human tumors. In salivary gland tumors (SGTs), little and conflicting information about the role of the estrogen receptor alpha (ERα), progesterone receptor (PgR) and androgen receptor (AR) has been described and in most cases the use of sex hormone antagonists is not contemplated in clinical practice. In this study, we analyzed a panel of sex hormone receptors that have not been widely investigated in SGTs-ERα, PgR, AR, but also ERβ and GPR30-to define their expression pattern and their prognostic and predictive value in a case series of 69 benign and malignant SGTs. We showed the aberrant expression of AR in mucoepidermoid and oncocytic carcinoma, a strong relation between cytoplasmic ERβ expression and tumor grade, and a strong correlation between nuclear GPR30 expression and disease-free survival (DFS) of SGT patients.

Background: Endocrine gland-derived vascular endothelial growth factor (Prok1) and prokineticin 2 (Prok2) are involved in the organ-specific regulation of angiogenesis, which is a crucial step toward cancer progression in most tumors, including those of thyroid gland. The oncogene BRAF V600E mutation is associated with poor clinical outcome of papillary thyroid cancer (PTC) and can independently predict its recurrence. Design: Our hypothesis was that Prok1 and Prok2 expression levels associated with BRAF mutations can be prognostic factors for PTC outcome. Prok1 and Prok2 were examined in PTC, a cell line derived from a human PTC (designated FB-2), euthyroid multinodular goiter (MNG), Graves’ disease (GD), and contralateral normal thyroid (NT) tissues from PTC cases. We evaluated BRAF mutation and its relationship with Prok1 expression pattern in PTC. Methods: We studied Prok1 and Prok2 mRNAs by real-time polymerase chain reaction and BRAF mutation by mutant allele-specific polymerase chain reaction amplification. Formalin-fixed, paraffin-embedded blocks of PTC and NT were used for the immunohistochemical determination of Prok1 using anti-endocrine gland vascular endothelial growth factor primary antibody. Results: Prok1 and Prok2 transcripts were both present in thyroid tissues, and Prok1 was differentially expressed in PTC compared to MNG, GD, and NT. Prok1 mRNA levels were very low in NT and MNG and significantly higher in PTC, FB-2, and GD ( p<0.05). Prok1 protein was almost undetectable in NT but was highly expressed in all PTC samples having an infiltrative pattern of growth and lymph node metastases ( p<0.05). Further, the expression of Prok1 in PTC was associated with 60% of the samples being positive for the BRAF mutation ( p<0.05). Conclusions: We found that Prok1 is significantly increased in PTC, and its expression in PTC is related to BRAF mutation. These results suggest that Prok1 could be a new useful marker for thyroid cancer progression. Prok1 therefore could also be a potential target for novel therapeutic strategies, although the lack of functional data suggests caution against generalization of this assumption.